Drug Industry Daily - April 27, 2010 Issue

FDA to Revise GMPs for Components to Protect
Supply Chain

The FDA is revising good manufacturing practice (GMP) regulations for
incoming raw materials to help industry secure the pharmaceutical
supply chain against economically motivated adulteration.

Revised regulations will significantly improve the control over
suppliers, Deb Autor, director of CDER’s Office of Compliance, said
Monday at the 2010 PDA/FDA Pharmaceutical Supply Chain Workshop in
Bethesda, Md. There is no timeline for the revisions, but they are
under way, she told DID.

Controlling the risk of counterfeit, adulterated or misbranded products
entering the supply chain “really comes down to each company thinking
very hard about what its potential vulnerabilities are and building
systems around that,” Autor told the audience. The FDA would like to
see industry be more proactive in predicting potential economically
motivated adulterants and designing test methods and supply chain
controls.

The FDA is finding that companies are failing to adequately control raw
materials — particularly physical characteristics such as particle
size and hydration — which contribute to the difficulty of reliably
producing a dosage form that performs consistently from batch to batch,
CDER Director Janet Woodcock said.

The agency is encouraging manufacturers to warn each other about
suppliers and materials that pose hazards. Companies also should notify
the FDA as soon as a problem is identified that could pose a health
risk.

“Folks have been reluctant,” she said. “People’s instinct is to just
drop the supplier and not talk about it.” Failing to act could damage
the industry’s credibility, she added.

Some companies are already working toward collaboration on supply chain
control. Martin VanTrieste, vice president of operations and quality
for Amgen, said that Johnson & Johnson unit Janssen-Cilag is
encouraging other companies to mimic its Drug Validation Portal, which
provides U.S. Customs and Border Protectionwith electronic
images of its product labels and packaging for comparison with incoming
shipments.

Similar photos can be used by a drug company’s own employees to help
screen incoming raw materials from suppliers, VanTrieste said.

Limited foreign supplier audits have also become a concern, Edwin
Rivera-Martinez, chief of the FDA’s International Compliance Branch,
said. Sometimes a company official, rather than a trained auditor, is
sent to the manufacturing site. That can be a problem because auditors
must be familiar with the manufacturing processes for ingredients,
Rivera-Martinez said. Even products that meet U.S. Pharmacopeia testing
standards may not have been manufactured under GMPs.

Among the solutions suggested by conference participants was auditing
suppliers’ control of the chain of ingredients as part of the
qualification procedure. Industry also noted more effort is needed to
train procurement employees to incorporate quality standards in
searches for suppliers.

The FDA is also acting to produce guidelines to promote safe supply
chains. A final version of the July 2009 draft guidance on
physical-chemical identifiers in solid oral dosage form drug products is
one such guidance, Ilisa Bernstein, director of pharmacy affairs in
the Office of the Commissioner, Office of Policy, said (DID,
July 14, 2009). — April Hollis

FTC: Ending Pay-for-Delay Settlements is Top Priority

The FTC is making its fight against pay-for-delay settlements between
brand- and generic-drug makers a top priority this year.

The patent settlements, in which brand companies reward generic-drug
makers to delay the introduction of less expensive versions of their
medicines, keep generic drugs off the market for an average of 17 months
longer than agreements without payments and will cost consumers and
taxpayers $35 billion over the next 10 years, the commission says in
its annual report.

The FTC also is pursuing actions against drugmakers in federal court
cases. In one case, the agency lodged a complaint against Cephalon in
2008, alleging the drugmaker paid four companies to refrain from
selling generic versions of its sleep drug Provigil (modafinil) until
2012 (DID,
Feb. 15, 2008).

The company entered into seemingly separate transactions worth a total
of more than $200 million, the FTC said in 2008 (DID,
May 23, 2008). For example, Teva Pharmaceuticals agreed not to
launch generic Provigil until April 2012 in exchange for a license
agreement relating to its modafinil patents and patent applications
worth up to $125 million in Provigil royalties. Cephalon also agreed to
buy modafinil active pharmaceutical ingredient from Teva at prices
higher than what it had been paying, the commission alleged at the
time.

The case is still pending in the U.S. District Court for the Eastern
District of Pennsylvania, the FTC says.

In a separate case, the commission obtained $2.1 million from
Bristol-Myers Squibb (BMS) for failing to inform the FTC of agreements
reached with Canadian drugmaker Apotex regarding potential generic
competition for blockbuster drug Plavix, the commission says in the
report. The commission charged that, as part of a patent settlement
with Apotex, BMS promised that it would not compete with Apotex during
the first 180 days that Apotex marketed its generic version of the
drug.

The agency suffered a defeat, however, in a case in which it claimed
reverse payment, or pay-for-delay, settlements Solvay Pharmaceuticals
made with Watson Pharmaceuticals, Par Pharmaceutical and Paddock
Laboratories for the marketing of generic AndroGel (testosterone)
violated federal antitrust laws.

The U.S. District Court for the Northern District of Georgia dismissed
the case in February, saying patent litigation is too complex and the
results too uncertain to assert such a claim (DID,
Feb. 25).

The agency had also hoped that a ban on the agreements would be
included in healthcare overhaul legislation signed into law earlier this
year, but the provision failed to be included in the final bill. Sen.
Herb Kohl (D-Wis.), however, has indicated that he will fight for his
pay-for-delay bill Preserve Access to Affordable Generics Act, S. 369,
to be considered as an individual piece of legislation by the full
Senate or piggyback on another bill (DID,
March 23).

Genentech Gets Untitled Letter for Consumer-Directed Herceptin Video

The FDA has issued an untitled letter to Genentech for a patient video
that overstates the efficacy of its breast cancer drug Herceptin and
minimizes its risks.

The consumer-directed video fails to present information about risks
associated with the chemotherapy drug with the same prominence as seen
in the presentation on the drug’s effectiveness, according to the letter
dated March 26 from the FDA’s Division of Drug Marketing, Advertising
and Communications.

Most of the 5 ½-minute video is a lively multimedia presentation with a
dramatic announcer’s voice and testimonials from Herceptin patients,
breast cancer awareness advocates, television news reports and an
oncology nurse, according to the letter. But the presentation of serious
risks associated with Herceptin (trastuzumab) is relegated to a
running telescript with no audio that rolls for 30 seconds before the
start of the video, the letter says.

The only risk information in the main part of the video is found in two
patient testimonials and omits discussion of the drug’s boxed warnings
regarding cardiomyopathy, pulmonary toxicity and infusion reactions,
the letter adds.

Patient testimonials in the video also imply the drug improves
long-term survival. For example, one woman says the drug allows her to
enjoy her son’s life “as he grows up.” However, clinical trials for
Herceptin plus chemotherapy as first-line therapy in patients with
metastatic breast cancer showed a median increase in survival of 4.8
months.

Genentech has formally responded to the letter and removed the video
from the Herceptin website, Genentech spokeswoman Krysta Pellegrino
told DID Monday. The company also is looking at other Herceptin
promotional materials, as well as promotional material for other
products, to ensure they are in compliance with FDA guidance in the
letter, she added.

Glenmark Wins Approval for Generic Progestin-Only Contraceptive

Glenmark Generics has received FDA approval of a generic formulation of
Watson Laboratories’ Nor-QD oral contraceptive.

The company will begin distributing the progestin-only oral
contraceptive in 0.35-mg tablets immediately, Glenmark said Monday. Its
generic norethindrone will be sold under the name Heather.

The approval marks the first time an India-based company has won
approval for a hormone product, Glenmark spokesman Jason D’Souza told DID
Monday. The FDA approval also is the first for a Glenmark product
manufactured at its Goa, India, hormone facility, according to the
company.

The U.S. market size for the approved product is $38 million, D’Souza
said. The company has another six hormone products awaiting FDA
approval, he added. — Owen Skoler

Nycomed, Merck Sign Commercialization Pact for COPD Drug Candidate

Nycomed will make and distribute its Daxas (roflumilast), the companies
said Monday. The drugmaker will receive an undisclosed upfront fee and
is eligible for milestone payments based on regulatory and
commercialization events.

Marketing applications for Daxas were filed with the European Medicines
Agency (EMA) and Health Canada last year. The EMA’s Committee for
Medicinal Products for Human Use recommended approval of the drug last
week. If approved, Daxas, a once-a-day oral tablet, will be the first
oral anti-inflammatory treatment for COPD patients, Nycomed and Merck
said.

In the UK, Merck will have exclusive commercialization rights, and
Nycomed will supply the finished product and have an option to
co-promote the drug.

In the U.S., Nycomed’s NDA for Daxas was acquired by Forest Research
Institute, but the drug failed to muster the votes for a recommendation
from an FDA panel this month (DID,
April 8). The Pulmonary-Allergy Drugs Advisory Committee suggested
Forest conduct clinical trials comparing Daxas with existing COPD
treatments, such as inhaled corticosteroids, to obtain more data. —
David Belian

China Counts More Than 600,000 Adverse Drug Events in 2009

China’s State Food and Drug Administration (SFDA) has published its
first annual report on adverse drug reaction (ADR) monitoring, noting
more than 600,000 reports of ADRs last year.

Fifty-five percent of the ADR reports were associated with
anti-infective drugs. The SFDA issued six ADR information bulletins for
adverse events related to acyclovir; clindamycin injection;
cefoperazone sodium and sulbactam sodium, a broad-spectrum
antibacterial agent; levofloxacin injection; and several traditional
medications. Another 8 percent of the reports involved cardiovascular
drugs.

The SFDA suspended sales by two Chinese companies of an herbal product
widely used to treat inflammatory conditions and withdrew marketing
authorization for bulk fenfluramine HCl drugs and formulations and
another traditional medicine. The agency also requested modifications to
10 package inserts because of changes in the drugs’ specifications.

Injectable drugs for all conditions accounted for almost 60 percent of
ADR reports, 37 percent involved oral preparations and 4 percent were
listed as “other.” The annual report also includes medication safety
tips and a Q&A on adverse drug event reporting.

Drug companies contributed just over 12 percent of the reports, though
the proportion is rising, SFDA says. Hospitals and other medical
institutions were responsible for about 85 percent of ADR reports last
year and 3 percent were made by individuals, the SFDA says.

In the U.S., the FDA logged 353,318 reports related to drugs and
biologics in its adverse events reporting system in the first three
quarters of last year. — Meg Bryant